Tapentadol (i.e., 3-[(1R, 2R)-3-(dimethyamino)-1-ethyl-2-methylpropyl] phenol) is a small organic molecule that is used as an analgesic. Tapentadol is known to have a dual mechanism of action as an agonist of the μ-opioid receptor and also as a norepinephrine (NE) reuptake inhibitor (NRI) for improved analgesic efficacy especially in chronic or neuropathic pain disorders.
Several different routes for preparing tapentadol have been reported. A typical method is to produce a racemic mixture of intermediates that must be separated by chiral chromatographic separation or by chiral resolution. The separation of chiral compounds, however, can be technically challenging, time consuming, or both.
There are a few asymmetric syntheses for the preparation of tapentadol that do not require chiral separation or chiral resolution, but rather relies on a direct asymmetric synthesis of chiral compounds. These syntheses can be moderately efficient. Yet, these syntheses consist of multiple reaction steps and have protection/deprotection steps of functional groups within the synthesis. Developing a more expedite synthetic process where no protecting groups are utilized or where a synthetic step is coupled with a deprotection step would provide a shorter synthesis, reduced cost, and a time savings.